The following proposal outlines our major interest in the role of intercellular communication in the regulation of ovarian function in mammals. Our investigations provide ample evidence for the modulatory role of both gonadotrophic and steroid hormones on the frequency and size of the pathways for cell-to-cell communication in the ovarian follicle and interstitial cell compartments. We will continue these investigations in order to (a) determine whether the ontogeny of the intercellular pathways termed gap junctions are preprogrammed or hormonally induced, (b) determine whether the modulatory effects of hormones on intercellular communication are the cause or the result of ovarian differentiation, (c) demonstrate the mode of gap junctions synthesis, assembly, and turnover, (d) determine whether communication-competent ovarian cells exhibit continuous coupling versus intermittent coupling as a function of cyclic hormonal stimulation, (e) determine whether the experimentally induced cystic ovary in rodents, which has been proposed as a model for the polycystic ovary condition in humans, may result from a qualitative or quantitiative intercellular communication failure and, if so, whether hormone therapy can restore normal cell communication and ovulatory function, (f) determine whether clomiphene citrate which is widely used to treat anovulatory disorders in humans is potentially harmful due to a possible hyperestrogenization of cells. These studies will make extensive use of cell and organ culture techniques in conjunction with quantitative freeze-fracture electron microscopy. It is hoped that the results of these studies will provide a better understanding of ovarian physiology which will ultimately lead to more effective treatments in the management of infertility disorders in humans and to the development of safe and effective contraception technologies.